Organ perfusion systems

ABSTRACT

An organ perfusion system comprises: a perfusion fluid circuit ( 16 ) arranged to circulate perfusion fluid through the organ; a surrogate organ ( 126 ) arranged to be connected into the circuit in place of the organ so that the circuit can circulate fluid through the surrogate organ; and organ sensing means arranged to distinguish between the presence of the organ in the circuit and the presence of the surrogate organ in the circuit. The sensing means may comprise one or more pressure sensors ( 136, 137, 138 ), or a flow meter ( 125 ). Further aspects relate to adjusting the content of at least one component, such as oxygen or a nutrient, in the perfusion fluid. Bubble detection means ( 113 ), and means ( 74 ) to measure the amount of fluid secreted by or leaked from the organ, may also be provided.

FIELD OF THE INVENTION

The present invention relates to perfusion systems for bodily organs, inparticular human organs, such as the liver, pancreas, kidney, smallbowel, but also other organs including non-human organs.

BACKGROUND TO THE INVENTION

It is known, for example from EP 1 168 913, to provide a system forextracorporeal organ perfusion in which a human or non-human organ canbe preserved, for example prior to transplant into a patient. The systemtypically comprises a reservoir for perfusion fluid, which may be bloodor another perfusion solution, and a circuit for circulating the fluidthrough the organ.

SUMMARY OF THE INVENTION

The present invention provides a perfusion system for the perfusion ofan organ, the system comprising a perfusion fluid circuit forcirculating perfusion fluid through the organ, adjustment means foradjusting the content of at least one component in the fluid, measuringmeans for measuring the content of said at least one component in theperfusion fluid, and control means arranged to control the adjustmentmeans. For example, the control means may be arranged to control theadjustment means so as to keep said measured content within a targetrange. In some cases that may be above a minimum target level, or belowa minimum target level, or between upper and lower target limits.

The content may be a relative content or a proportion, for example itmay be a percentage, and it may be measured by mass, or by volume, or bymole percent.

The at least one component may be at least one of: oxygen; carbondioxide; and a nutrient, such as glucose.

Where the at least one component comprises oxygen, the adjustment meansmay comprise oxygen adding means arranged to add oxygen into the fluid.For example it may comprise an oxygenator.

Where the at least one component comprises carbon dioxide, and theadjustment means may comprises carbon dioxide extraction means arrangedto extract carbon dioxide from the fluid. This may be arranged to supplyair, or another gas, which can absorb or extract carbon dioxide from thefluid. This function can be performed by an oxygenator which alsosupplies oxygen, or it can be performed by a separate device or system.

The at least one component may comprise at least one of, or both of:oxygen and carbon dioxide, in which case the system may further comprisenutrient measuring means arranged to measure the content of at least onenutrient in the fluid. The system may comprise a nutrient supply. Thesystem may comprise nutrient adding means arranged to add the nutrient,for example from the supply, into the fluid. The control means may bearranged to control the nutrient adding means to add the nutrient if thecontent of the nutrient falls below a target range.

The system may comprise a thermometer arranged to measure thetemperature of the fluid. The system may comprise thermal adjustmentmeans arranged to adjust the temperature of the fluid. The control meansmay be arranged to control the thermal adjustment means to maintain thetemperature of the fluid within a target range.

The system may comprise an analysis duct through which the fluid canflow. The measuring means may be arranged to measure the fluid in theanalysis duct. For example the analysis duct may connect two parts ofthe circuit which will experience different pressures, from each other,during perfusion. This will tend to cause some of the fluid to flowthrough the analysis duct during perfusion. For example the analysisduct may have an upstream end connected into the circuit upstream of theorgan, and a downstream end connected to the circuit downstream of theorgan.

The measuring means may be arranged to operate during perfusion of theorgan. The control means may be arranged to operate during perfusion ofthe organ to maintain the target range or ranges.

The control means may include a memory arranged to store at least onelimit of said range, or of at least one of said ranges. The controlmeans may be arranged to compare the measured content with said at leastone limit. This can enable it to determine when the measured content isoutside the target range.

The system may comprise a user interface arranged to enable a user toinput at least one limit of said range, or of at least one of saidranges. The user interface may also be arranged to indicate the contentof at least one of the components of the fluid.

The system may comprise organ sensing means arranged to detect thepresence of the organ in the circuit. The system may further comprise asurrogate organ arranged to be connected into the circuit in place ofthe organ so that the circuit can circulate fluid through the surrogateorgan. Where the system includes organ sensing means, the organ sensingmeans may be arranged to distinguish between the presence of the organin the circuit and the presence of the surrogate organ in the circuit.

Indeed, the present invention further provides a perfusion system forperfusing an organ, the system comprising: a perfusion fluid circuitarranged to circulate perfusion fluid through the organ; a surrogateorgan arranged to be connected into the circuit in place of the organ sothat the circuit can circulate fluid through the surrogate organ; andorgan sensing means arranged to sense the presence of the organ, or thesurrogate organ, or both, in the circuit. The organ sensing means maythereby be arranged to distinguish between the presence of the organ inthe circuit and the presence of the surrogate organ in the circuit.

The organ sensing means may comprise at least one pressure sensorarranged to measure the pressure of the perfusion fluid at at least onepoint in the circuit. The organ sensing means may be arranged to measurethe difference in pressure between two points in the circuit. The organsensing means may comprise a pressure sensor arranged to measure thepressure of perfusion fluid flowing towards the organ. The organ sensingmeans may comprise a pressure sensor arranged to measure the pressure ofperfusion fluid flowing away from the organ. Alternatively, or inaddition, the organ sensing means may comprise a flow meter arranged tomeasure the rate of fluid flow at at least one point in the circuit. Theorgan sensing means may further be arranged to receive data regardingthe speed of a pump in the circuit, and to use that data in determiningwhether the organ or the surrogate organ is present in the circuit.

The control means may be arranged to operate in two different modes, oneof which is a preparation mode suitable for preparing the system forperfusion of an organ, and one of which is a perfusion mode suitable forperfusion of an organ. The control means may be arranged, in both of themodes, to control the content of at least one component of the perfusionfluid. The control means may be arranged to control the fluid flow inthe perfusion circuit in a different way in each of the two modes. Forexample in one mode the fluid may be pumped at constant speed.

The system may comprise a bubble detection means arranged to detectbubbles in the fluid during perfusion.

Indeed the present invention further provides a perfusion systemcomprising a circuit for circulating perfusion fluid through the organ,control means arranged to control the flow of fluid round the perfusioncircuit, and bubble detection means arranged to detect the presence ofbubbles in the fluid.

The control means may be arranged to respond to detection of bubbles bythe bubble detection means. For example the control means may bearranged to respond to detection of the bubbles by producing a warningoutput, such as by displaying a warning. Alternatively, or in addition,it may be arranged to respond by reducing the fluid flow through atleast one part of the circuit, or into the organ, optionally stopping itcompletely, for example by partially or completely closing a flowcontrol valve. The flow control valve may be arranged to control flow offluid from a reservoir to the organ.

The bubble detection means may be arranged also to measure the flow rateof fluid in the perfusion circuit. The bubble detection means comprisesan ultrasound transducer. The bubble detection means may be arranged todetermine both whether bubbles are present in the fluid and the flowrate of the fluid from the timing of ultrasound transmissions anddetections.

The system may comprise measuring means arranged to measure the amountof fluid secreted by or leaked from the organ. For example the fluid maybe bile from a liver, ascites from a liver, urine production from thekidney or any other excretion from any organ.

The system may further comprise a sump arranged to collect the secretedor leaked fluid. The measuring means may be arranged to measure thevolume of fluid that enters the sump. The system may be arranged torecord and display the amount of fluid that is secreted or leaked. Forexample the control means may include part of the measuring means, andmay be arranged to calculate and record the total volume of the fluid,or the rate of flow of the fluid, or both, and may record these atregular intervals during perfusion to monitor the organ. The controllermay be arranged to generate a display of all or part of thisinformation. The controller may be arranged to modify its control of atleast one component of the system in response to the measured volume orthe measured flow rate. For example it may be arranged to vary thespeed, or the average speed, or the duty cycle, of a pump which isarranged to pump the fluid from the sump.

The system may further comprise a support stand on which at least someof the components of at least one of the perfusion circuit, theadjustment means and the control means are mounted. The system mayfurther comprise a transport system on which the support stand can bemounted. The transport system may include a cover arranged to cover thesupport stand and the components mounted on it. The transport system mayinclude a wheeled base. The transport system may be arranged to supportthe support stand in transport position, or an operative position whichis raised relative to the transport position.

Some embodiments of the present invention can provide a perfusion systemin which one or more of the following functions are automated: detectionof an organ in the circuit for perfusion; detection of perfusion fluidin the circuit; control of fluid pressure in the circuit duringperfusion; control of fluid temperature in the circuit during perfusion;and control of one or more nutrients in perfusion fluid duringperfusion. The system may therefore be fully automated.

Some embodiments of the invention provide a system that is portable.

Some embodiments may be arranged to be battery and mains powered.

The present invention further provides a method of perfusing an organ,the method comprising circulating perfusion fluid through the organ,measuring the content of at least one component in the perfusion fluid,and adjusting the content of said at least one component in the fluid soas to keep said measured content within a target range. The content maybe a relative content or a proportion, for example it may be apercentage, and it may be measured by mass, or by volume, or by molepercent. The at least one component may be at least one of: oxygen;carbon dioxide; and a nutrient, such as glucose. The measurement or theadjustment may be performed using any system according to the inventionas described above.

Preferred embodiments of the present invention will now be described byway of example only with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a perfusion system according to anembodiment of the invention;

FIG. 2 is an enlargement of part of FIG. 1;

FIG. 3 is a schematic diagram of an oxygenator forming part of thesystem of FIG. 1;

FIG. 3 a is a diagram of a combined flow meter and bubble detectoraccording to an embodiment of the invention and forming part of thesystem of FIG. 1;

FIG. 4 is a schematic diagram of an oxygen concentrator forming part ofthe system of FIG. 1;

FIG. 5 is a diagram similar to FIG. 2 showing a liver connected into thesystem of FIG. 1;

FIG. 6 is a diagram of the system of FIG. 1 modified for perfusion of asingle input—single output organ, such as a pancreas or kidney;

FIGS. 7 a, 7 b and 7 c are perspective views of the system of FIG. 1mounted in a mobile transportation system according to an embodiment ofthe invention;

FIGS. 8 a, 8 b and 8 c are perspective views of the system of FIG. 1mounted in a mobile transportation system according to a furtherembodiment of the invention;

FIGS. 9 a, 9 b, 9 c and 9 d are perspective views of the system of FIG.1 mounted in a mobile transportation system according to a furtherembodiment of the invention; and

FIG. 10 is a perspective view of the system of FIG. 1 mounted in afurther alternative mobile transportation system.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIGS. 1 and 2, a perfusion system according to anembodiment of the invention generally comprises a sling 10 on which anorgan can be supported, a fluid reservoir 12, an oxygenator 14, and aperfusion circuit 16 arranged to circulate fluid between the reservoir,the organ, and the oxygenator during perfusion. A controller 18 isarranged to control the functioning of the system as will be describedin more detail below.

The sling 10 is of moulded plastics or other suitable material anddesigned to be compliant so as to enable non-traumatic support of theorgan whilst providing a degree of shock absorption during transport.The sling 10 has a perforated base 19 through which fluids leaking fromthe organ can flow out, and side walls 20 extending upwards from thebase 19, and a rim 22 extending around the top of the side walls 20. Afluid sump 24 which, where the organ is a liver, forms an ascites sump,is located beneath the sling 10, and comprises a concave base 26 thattapers downwards to a drainage hole 28, which is formed through itslowest point. The sump 24 is arranged to catch fluid leaking through thebase 19 of the sling. The sump 24 also comprises side walls 30 thatextend upwards from the base 26, around the side walls 20 of the sling,and have a flange 32 around their top which supports the rim 22 of thesling 10. A removable cover 34, which is of moulded plastics, fits overthe top of the sling 10 and has a rim 36 around its lower edge whichfits against the rim 22 of the sling.

The sling 10 is supported within an organ container 40 which has theascites sump 24 and a bile sump 42 supported in its base 44, and in thisembodiment formed integrally with it. The organ container 40 has sidewalls 46 extending upwards from its base 44 and a removable cover 48.The bile sump 42 is about twice as deep as the ascites sump 24 andgenerally narrow and tubular in shape, and extends downwards from thebase 44 of the container 40 with its rim 52 level with the rim 32 of theascites sump 24 and the rim 22 of the sling.

The bile sump 42 is formed in two parts, an upper part 42 a and a lowerpart 42 b, both of which are integral with the base 44 of the organcontainer. The lower part 42 b has a bile inlet port 54 formed in itsside, towards its upper end 56, and a bile overflow port 58 formed inits upper end. A bile outlet port 60 is formed in the base 44 of theorgan container close to the top of the bile sump, with an upperconnector 60 a for connection via a cannula to the liver, and a lowerconnector 60 b for connection to a bile measurement system 62. The bilemeasurement system 62 is arranged to measure the volume of bile secretedby the liver before allowing it to flow into the bile sump 42.

As can best be seen in FIG. 2, the bile measurement system 62 comprisesa bile receiving duct 64 having its upper end connected to the lowerconnector 60 b, and its lower end connected to a T-piece connector 66, abile outlet duct 68 having its upper end connected to the connector 66and its lower end connected to the bile sump inlet port 54, and anoverflow duct 70 having its lower end connected to the connector 66 andits upper end connected to a further port 69 formed in the base 44 ofthe container. An overflow pipe 72 connects the top of the further port69 to the bile overflow port 58 in the top of the lower part 42 b of thesump. A liquid level sensor 74 is arranged to measure the level of fluidin the overflow duct 70 and to output a signal indicative of the fluidlevel to the controller 18. In this embodiment the liquid level sensor74 is arranged to detect when the liquid level in the overflow duct 70reaches a predetermined height, and send a signal indicative of this tothe controller 18. A flow control valve, which in this embodimentcomprises a pinch valve 76, in the bile outlet duct 68 is switchablebetween a closed state in which it closes the outlet duct 68 so thatbile can build up on the measurement system 62 and an open state inwhich it allows bile to drain from the measurement system 62 into thebile sump 42. The controller 18 is arranged to control the flow controlvalve 76.

The controller 18 is arranged to measure the rate at which bile issecreted by the liver by closing the pinch valve 76 so that bile buildsup in the outlet duct 68, and then in the bile receiving duct 64 andoverflow duct 70. When the level sensor 74 detects that the bile hasreached the predetermined level, it is arranged to send a signal to thecontroller 18 which responds by opening the pinch valve 76, for examplefor a predetermined period, to allow the bile to drain out of themeasurement system into the sump, and then closes it again so that bilecan start to collect in the measurement system again. The controller 18is also arranged to record in memory the times at which the bile reachesthe predetermined level, and therefore the times at which themeasurement system is filled. This information, together with the knownvolume of the system when it is filled to the predetermined level,allows the rate at which bile secreted over time to be monitored. Forexample the controller 18 may be arranged to calculate a flow rate eachtime the valve 76 is opened from the known volume of the system and thetime interval between the valve opening and the previous valve opening.That flow rate can be displayed on the GUI 17, being updated each time anew calculation of flow rate is recorded. Alternatively the controller18 may be arranged to store this flow rate information in memory, sothat flow rate data for the whole perfusion process can be stored andthen output or displayed via the GUI 17. As a further alternative, thecontroller may not perform any calculation but may generate an outputwhich varies with the flow rate, and the GUI may be arranged to respondto the output by generating a display, such as a line graph, which isindicative of the flow rate, for example by having appropriately markedaxes. It will be appreciated that, for organs other than the liver, thismeasurement system can be arranged to measure other fluids leaking from,or excreted by, the organ during perfusion, and to record and displaythe measured volume. For example the organ may be a kidney and the fluidmay be urine.

Referring back to FIG. 1, an ascites duct 80 is connected at one end tothe drainage hole 28 in the bottom of the ascites sump 26 and at theother end to an ascites return port 82 in the top of the fluid reservoir12. The ascites duct 80 has a central portion 80 a that is the lowestpart of the duct 80, being below the level of the ascites sump 26, aswell as below the level of the reservoir 12. An ascites pump 84 isprovided in the central portion 80 a of the ascites duct 80 to pumpascites from the sump 26 back up into the reservoir 12. An ascitesmeasurement tube 86 extends vertically upwards from the central portion80 a of the ascites duct, adjacent to, and upstream of, the pump 84, andhas a fluid level sensor 88 in it. This level sensor 88 is arranged todetect, and output a signal, when fluid in the measurement tube 86reaches a predetermined level that is below the base 19 of the sling 10,and in this embodiment above the drainage port 28 in the ascites sump.The fluid level sensor 88 is connected to the controller 18 whichreceives the signals from it, and can therefore detect when the level ofascites in the sump reaches a predetermined level. In response to thisthe controller 18 is arranged to activate the ascites pump 84, forexample for a predetermined time, to reduce the level of ascites in thesump 26. The speed of the pump 84 may be variable and the controller 18may be arranged to control the speed of the pump, or the duty ratio ofthe pump, or the average speed of the pump, on the basis of the measuredfluid level. In other embodiments the ascites level sensor can belocated within the sump 26. Indeed any suitable system for measuring thevolume of accumulated ascites can be used as feedback to control theoperation of the pump 84. For example a pressure sensor located close tothe pump 84 could be used to measure accumulated ascites volume. Instill other embodiments the ascites pump 84 can simply be arranged tooperate for fixed periods with no measurement of ascites volume.

In a modification to this embodiment, there is a further ascites levelsensor in addition to the sensor 88, so that the sensors can detect whenthe ascites level reaches upper and lower levels. The controller 18 isarranged to start the ascites pump 84 when the ascites is detected asreaching the upper level, and to step the ascites pump 84 when theascites level drops to the lower level. The controller is then arrangedto record the timing of each time the pump is turned on, and thisprovides an indication of the total volume of ascites and the flow rateof ascites during perfusion. This information can be stored anddisplayed on the GUI 17 in the same way as the bile measurements. Thespeed of the pump 84 may be variable and the controller 18 may bearranged to control the speed of the pump, or the duty ratio of thepump, or the average speed of the pump, on the basis of the measuredfluid level. It will be appreciated that, for other organs, thismeasurement system can be used to measure the total volume or flow rateof other fluids leaking from, or excreted by, the organ duringperfusion. This measurement can also be provided with only one asciteslevel sensor as shown in FIG. 1, for example if the pump 84 is arrangedto operate until it has pumped all of the ascites that is upstream ofthe pump 84, which can be assumed to be a fixed volume.

The perfusion circuit 16 further comprises a first fluid supply duct100, which when used for perfusion of a liver forms a portal duct, asecond fluid supply duct 102, which when used for perfusion of a liverforms a hepatic artery duct, and a fluid removal duct 104, which whenused for perfusion of a liver forms an inferior vena cava (IVC) duct.The system and its operation will now be described for perfusion of aliver, but it will be appreciated that it can equally be used for otherorgans, in particular single-inflow single-outflow organs such as thekidney, small bowel or pancreas if arranged as per the alternativeconfiguration of FIG. 6. The portal duct 100 has one end connected to anoutlet port 106 in the fluid reservoir and the other end attached to aportal vein connector 108. The portal duct 100 extends through a port110 in the side wall 46 of the organ container 40 so that the portalvein connector 108 is located inside the container. A flow control valve112, in the form of a pinch valve, having a variable degree of opening,is provided in the portal duct 100 and is connected to the controller18. The controller 18 is arranged to vary the degree of opening of thepinch valve 112 so as to control the rate of flow of fluid from thereservoir 12 to the portal vein of a liver. A portal flow sensor 113 isprovided in the portal duct 100 and is arranged to output a signalindicative of the flow rate of fluid in the portal duct 100. The outputof the flow sensor 113 is connected to the controller 18 which cantherefore monitor the flow rate in the portal duct. The controller 18 isalso arranged to determine from the flow sensor 113 signal when the flowof fluid from the reservoir ceases due to the reservoir being empty. Inresponse to detection of an empty reservoir the controller 18 isarranged to close the flow control valve 112 so as to prevent air fromreaching the organ and to enable replenishment of the perfusion fluidvolume within the reservoir. The flow sensor in this embodiment is alsoarranged to act as a bubble detector, arranged to output a signalindicative of the presence of air bubbles in the fluid in the portalduct 100. The controller 18 is arranged to close the flow control valve112 on detection of bubbles in the same way as if it detects acompletely empty reservoir on the basis of fluid flow. The hepaticartery duct 102 has one end connected to a first outlet port 114 of theoxygenator 14 and the other end attached to a hepatic artery connector116. The hepatic artery duct 102 extends through a port 118 in the sidewall 46 of the organ container 40 so that the hepatic artery connector116 is located inside the container. The IVC duct 104 has one endattached to an IVC connector 120, which is located inside the container40, and extends out through a port 122 in the base 44 of the organcontainer 40, having its other end connected to an inlet port 124 of theoxygenator 14.

A pump 123 is provided in the IVC duct 104 having its inlet connected bya part of the IVC duct 104 to the IVC connector 120, and its outletconnected to the inlet port 124 of the oxygenator 14. The pump 123 isarranged to pump fluid from the IVC duct 104 into the oxygenator 124.The pump 123 is a variable speed pump and is connected to, andcontrolled by, the controller 18. An IVC flow sensor 125 is arranged tomeasure the rate of fluid flow rate in the IVC duct 104 and is arrangedto output a signal indicative of the flow rate of fluid in the vena cavaduct 104. The output of the flow sensor 125 is connected to thecontroller 18 which can therefore monitor the flow rate in the IVC duct104.

Each of the connectors 108, 116, 120 is a quick-release connectorarranged to allow the duct to which it is attached to be connected,either via a cannula to the appropriate vein or artery of the liver, orto a surrogate organ 126 which is arranged to complete the perfusioncircuit prior to connection of the real organ. The surrogate organ 126comprises two inlet ducts 128, 130 for connection to the portal duct 100and the hepatic artery duct 102, and one outlet duct 132 for connectionto the IVC duct 104. In this embodiment the surrogate organ is in theform of a simple Y-piece connector 134 which connects the two inletducts 128, 130 to the outlet duct 132 so that, when it is connected intothe circuit, fluid can flow through it from the portal duct 100 and thehepatic artery duct 102 to the IVC duct 104.

Each of the portal duct 100, the hepatic artery duct 102 and the IVCduct 104 has a pressure sensor 136, 137, 138 in it, arranged to measurethe pressure of fluid in the duct 100, 102, 104. Each of these pressuresensors 136, 137, 138 is arranged to measure pressure at a point closeto the respective connector 108, 116, 120, and to output a signalindicative of the pressure at that point. In this embodiment, each ofthe ducts 100, 102, 104 is split into two sections and each of thepressure sensors 136, 137, 138 is located in a moulded plastics sensorbody which also serves to connect the two sections of the duct together.The sensors 136, 137, 138 are each located just outside the wall 46 orthe base 44 of the organ container 40. In each case the duct between thepressure sensor 136, 137, 138 and the connector 108, 116, 120 is ofsubstantially constant cross section, so the pressures sensed by thesensors 136, 137, 138 are approximately equal to the pressure of fluidflowing into and out of the surrogate organ, or the actual organ whenthat is connected into the circuit.

The oxygenator 14 has a second outlet port 140 which is connected by apressure control duct 142 to a pressure control port 144 in the fluidreservoir 12. A flow control valve, in the form of a pinch valve 146,having a variable degree of opening, is provided in the pressure controlduct 142 and is connected to the controller 18 so that the controllercan vary the degree of opening of the pinch valve 146 thereby to controlthe return flow of fluid from the oxygenator 14 to the reservoir 12.This, together with the speed of the pump 123, is controlled by thecontroller 18 to control the pressure of fluid flowing to the organthrough the hepatic artery duct 102, as well as the pressure of thefluid in the vena cava duct 104 flowing away form the organ.

Referring to FIG. 3, the oxygenator 14, which is shown schematically,comprises a through duct 150 arranged to carry fluid from the inlet port124 to the two outlet ports 114, 140. An oxygen chamber 152 has an inletport 154 for connection to an oxygen supply and an air supply, and anoutlet or vent port 156 for venting the oxygen and air from the oxygenchamber. A vent 158 is connected at its lower end to the through duct150 and extends upward so that its upper end is approximately level withthe top of the reservoir 12. This vent 158 is closable, and is arrangedto be opened during filling of the fluid circuit to vent air from theoxygenator, but is closed during perfusion. A permeable membrane 160between the oxygen chamber 152 and the through duct 150 allows oxygen inthe oxygen chamber 152 to oxygenate fluid, which may be blood, in thethrough duct 150, and allows air in the oxygen chamber 152 to carry awayCO₂ from the fluid. A water chamber or duct 162 is also connected to awater inlet port 164 and a water outlet port 166, and is separated fromthe through duct 150 by a thermally conductive wall 168. This provides aheat exchanger which allows water, or another suitable thermal controlfluid, to be circulated through the oxygenator 14 to control thetemperature of the perfusion fluid. A heater 167, such as a Peltierheater, is provided to heat water entering the oxygenator via the waterinlet port 164, and a thermometer 169 a is provided to measure thetemperature of the perfusate flowing out of the oxygenator into thehepatic artery duct 102. A further thermometer 169 b is arranged tomeasure the temperature of the water that is supplied to the heatexchanger. The heater 167 and the thermometers 169 a, 169 b areconnected to the controller 18 which is arranged to measure and monitorthe temperature of the perfusate supplied to the organ and the watersupplied to the heat exchanger, and control the heater 167 so as tomaintain the perfusate temperature at a desired level, for examplewithin a target temperature range.

It will be appreciated that other devices can be used for adding oxygento, and extracting carbon dioxide from, the perfusate. For example abubbler can be used, instead of the type of oxygenator shown in FIG. 3,which bubbles the concentrated oxygen through the perfusate. Also,instead of one device which brings a gas into contact with the perfusateand in which the oxygen and carbon dioxide content of the gas arecontrolled, the system can include separate devices one for each gas.

Referring to FIG. 3 a the flow sensor 113 in the portal duct 100 is, asdescribed above, also arranged to act as a bubble detector. In thisembodiment the flow sensor 113 comprises a housing 300 arranged to beclipped around the conduit, in this case the portal duct 100. Twoultrasound transducers 302, 304 are supported in the housing 300 andarranged so that they are located on one side of the conduit. Areflector 306 is supported in the housing 300 and arranged to be locatedon the opposite side of the conduit from the transducers 302, 304. Thetransducers 302, 304 are offset from each other along the conduit in thedirection of fluid flow, and angled so that when each of them transmitsan ultrasound signal it will be reflected from the reflector 304 ontothe other transducer, such that it can be detected. Each transducer 302,304 is arranged to emit a series of pulses of ultrasound, and the timingof the pulses is controlled so that the two transducers 302, 304 emitpulses alternately, with the non-emitting transducer being arranged todetect the emitted pulse after it has been reflected from the reflector306. The time taken for ultrasound to travel in each direction betweenthe two transducers is measured, using the emission and detection times,and the detector 145 is arranged to determine the difference between thetransmission times in the two directions and from that difference tocalculate the flow rate of fluid in the conduit 102. If gas bubbles arepresent in the perfusate these reflect ultrasound back to the transducerthat transmitted it and, in some cases, reflect the ultrasound on to theother non-transmitting transducer so that they arrive at a differenttime from those reflected from the reflector 304, and generally at muchsmaller amplitudes. Therefore the bubble detector 145 is arranged toanalyse the detection signals from both of the transducers 302, 304 anddetermine from their timing and amplitude when bubbles are present inthe perfusate. The signals from the ultrasound detector can be processedlocally in a processor forming part of the bubble detector, so that theprocessor in the bubble detector sends a simple signal to the controller18 indicative of the presence of gas bubbles in the perfusate, or thedetector signals can be input directly to the controller 18 which can bearranged to analyse them to detect the presence of the gas bubblesitself.

In response to the detection of gas bubbles the controller 18 may bearranged to output a warning signal to the GUI which can be arranged toprovide a visual or audible warning on receipt of the warning signal. Inaddition, the controller is arranged to stop the flow of perfusate intothe organ via the portal duct if it determines that gas bubbles arepresent in the perfusate. Specifically in this case, in response to thedetection of bubbles in the portal duct 100, the controller 18 isarranged to close the pinch valve 112. It is also arranged to fully openthe pinch valve 146 for a fixed time period, to enable replenishment ofthe volume within the reservoir. Following this time delay it isarranged to re-open the pinch valve 112, and to re-set the valve 146 soas to achieve the desirable arterial pressure.

In other embodiments, the system may include a further bubble detectorin the hepatic artery duct or the IVC duct. In this case the controller18 is arranged, when gas bubbles are detected, to stop the pump 123 tostop the flow of fluid through the organ as well as to provide thewarning. This enables a user to take precautionary measures, such asallowing the gas bubbles to escape from the perfusate, or even todisconnect the organ and flush the gas bubbles form the fluid circuit,before re-starting perfusion.

In other embodiments, other types of bubble detector can be used. Forexample an ultrasound bubble detector can be used that is not combinedwith a flow rate sensor, and includes only a single transducer. In thatcase the flow rate sensor can be provided separately, and can be of adifferent form other than an ultrasound sensor.

Referring back to FIG. 1, a nutrient control circuit 170 comprises a setof syringes 172, in this case four, each containing a respectivenutrient, and a nutrient feed duct 174 which has one end connected to aseparate fluid reservoir 176 and the other end connected to a nutrientinlet port 178 in the top of the main fluid reservoir 12. Each of thesyringes 172 is connected to the nutrient feed duct 174 by a respectivenutrient input duct 180. A nutrient pump 182 is arranged in the nutrientfeed duct 174 to pump fluid through the nutrient feed duct from thenutrient feed reservoir 176 into the main reservoir 12 via the nutrientinlet port 178. The pump 182 and the syringes 172 are controlled by thecontroller 18 so that the rate at which each of the nutrients is fedinto the reservoir 12 is controlled.

A small diameter fluid analysis duct 190 has one end connected to theIVC duct 104, upstream of the pump 123, and in this case downstream ofthe IVC flow sensor 125, and the other end connected to the pressurecontrol duct 142, upstream of the pressure control valve 146, so thatfluid can flow through the fluid analysis duct 190 from the pressurecontrol duct 142 to the IVC duct 104, bypassing the organ. A measurementsystem, in this case in the form of a blood gas analyser (BGA) 192 isarranged to measure various parameters of the fluid flowing through thefluid analysis duct 190. In this embodiment the BGA 192 is arranged tomeasure the oxygen content and the carbon dioxide content of the fluidflowing through it. Other parameters, including any one or more oftemperature, pH, base excess, potassium, glucose, haematocrit and oxygensaturation can also be measured and monitored. The BGA 192 is connectedto the controller 18 and arranged to output signals each of which isindicative of the value of one of the parameters it measures, and thecontroller 18 is arranged to receive those signals so that theparameters can be monitored by the controller 18. The signals thereforeinclude an oxygen level signal and a CO₂ level signal in thisembodiment.

A priming bag or reservoir 194 is supported at a level which is abovethe top of the reservoir 12, and connected by a priming duct 196 to theperfusion circuit at a priming point which is in the vena cava duct 104at its lowest point 104 a. This is also the lowest point of theperfusion circuit 16, which allows the whole circuit 16 to be filledfrom the bottom, as will be described in more detail below.

Referring to FIG. 4, the oxygen supply to the oxygenator inlet 154 isprovided by an oxygen concentrator 200. This comprises a pair of zeolitetowers 202, 204, an air inlet 206 arranged to receive gas in the form ofair at atmospheric pressure, a compressor 208 arranged in the inlet tocompress the incoming air, and a two way switch valve 210 operable tocontrol the flow of incoming air into the zeolite towers 202, 204. Eachof the towers 202, 204 has an outlet 212, 214 and these are connectedtogether to form a single outlet from the oxygen concentrator which inturn is connected to the inlet 154 of the oxygenator. In use, as thecompressed air flows through the zeolite towers 202, 204, the zeoliteextracts nitrogen from the air which increases the concentration ofoxygen in the gas. The nitrogen leaves the towers via vents 216, and thegas leaving the concentrator 200, which comprises concentrated oxygen aswell as some nitrogen and traces of other gases, is fed to theoxygenator inlet 154. A proportional valve 224 in the outlet from theoxygen concentrator is arranged to control the flow rate of gas, andhence oxygen, from the oxygen concentrator 200 to the oxygenator 14. Theproportional valve 224 is connected to, and controlled by, thecontroller 18 so that the controller can control the flow rate of oxygeninto the oxygenator 14. The air supply to the oxygenator inlet 154 isprovided by a further compressor 220 which has an inlet 222 arranged toreceive air at atmospheric pressure. A further proportional valve 226 inthe outlet from the compressor 220 is connected to and controlled by thecontroller 18, so that the controller can control the flow rate of airfrom the compressor 220 to the oxygenator, and hence the rate ofextraction of carbon dioxide.

In a modification to the arrangement of FIG. 4, the second compressor220 is omitted and the output from the first compressor 208 is connectedboth to the oxygen concentrator 200 and through a separate air duct viathe second proportional valve 226 to the oxygenator gas inlet. Thesingle compressor 208 therefore provides the pressure for the oxygen andair supplies, the flow rates of which are controlled independently bytheir respective flow control valves 224, 226.

Referring to FIG. 5, when the system is in operation for perfusing aliver, the surrogate organ 126 is removed, and the liver 250 to beperfused is placed in the sling 10. The portal vein, hepatic artery,inferior vena cava (IVC), and bile duct of the liver are cannulated, andthe cannulae connected to the portal vein connector 108, the hepaticartery connector 116, the vena cava connector 120, and the bile outletport 60 respectively.

Referring back to FIG. 1, during perfusion, when the system is operatingin a perfusion mode, perfusate fluid flow through the liver iscontrolled by the controller 18 which is arranged to controlling thepressure in the hepatic artery duct 102 and the IVC duct 104 to maintainthem at approximately constant pressures, allowing the liver to regulatethe flow rate of fluid through itself. To do this, the controller 18 isarranged to monitor the pressure in the hepatic artery duct 102 bymonitoring the output signal from the pressure sensor 137 and thepressure in the IVC duct 104 by monitoring the output of the pressuresensor 138, and to control the perfusion pump 123 and the pinch valve146 in the pressure control duct 142 so as to maintain the measuredpressures, i.e. the pressure sensor output signals, at respective setlevels, or within respective ranges.

The oxygen level in the perfusate fluid is also controlled by thecontroller 18 during perfusion. While most of the oxygenated perfusatefrom the oxygenator outlet 114 flows through the hepatic artery duct102, a small proportion of it is diverted through the fluid analysisduct 190 and through the BGA 192. The BGA 192 detects the level ofoxygen in the perfusate, which is monitored by the controller 18. Thecontroller 18 is arranged to control the pressure and flow rate ofoxygen supplied by the oxygen concentrator 200 to the oxygenator bycontrolling the pump 208 and the two-way valve 210 of the oxygenconcentrator 200, so as to control the rate at which perfusate isoxygenated in the oxygenator 100. The controller 18 is arranged to keepthe oxygen level of the blood at a predetermined level or within apredetermined range. The controller 18 has a memory in which a targetlevel or range of the oxygen content can be stored and the controller isarranged to compare the measured level with the stored level todetermine how the oxygen level needs to be controlled. The stored targetlevel can be selected and altered by means of a user input which in thiscase is in the form of a graphic user interface (GUI) 17 connected tothe controller 18. The GUI 17 is also arranged to display variousinformation including the values of various operating parameters of thesystem. These can include oxygen level in the perfusion fluid, carbondioxide level in the perfusion fluid, temperature of the perfusionfluid, the level of any nutrient in the perfusion fluid, such asglucose.

The carbon dioxide (CO₂) level in the perfusate is also monitored andcontrolled by the controller 18 during perfusion in a similar way to theoxygen level, with the controller 18 continuously using the CO₂ levelsignal from the BGA 192 to measure the CO₂ level in the perfusate,comparing it with target levels stored in memory in the controller 18,and controlling the air flow control valve 226 to control the flow rateof air into the oxygenator 16. The target CO₂ level can also be set andadjusted by a user by means of the user input 17.

The temperature of the perfusate supplied to the organ is monitored andcontrolled by the controller 18 which is arranged, during perfusion, tomonitor the signal from the perfusate thermometer 169 a and the waterthermometer 169 b and control the water heater 167 to control thetemperature of water flowing in the heat exchanger, and optionally alsothe flow rate of water flowing through the heat exchanger, thereby tomaintain the perfusate temperature within a target temperature range.This target range is stored in memory in the controller 18 and can beset and adjusted by means of the user input 17.

The level of each of the monitored nutrients in the perfusate is alsomonitored and controlled by the controller 18 during perfusion in asimilar way to the oxygen level, with the controller 18 using thenutrient level signal from the BGA 192 to measure the nutrient level inthe perfusate, comparing it with target levels stored in memory in thecontroller 18, and controlling the appropriate syringe 172 to add thenutrient if the nutrient level falls below a predetermined level. Theaddition of nutrients will generally be intermittent, so syringe 172 canbe controlled simply to add a predetermined amount of the nutrient ifthe nutrient level in the perfusate falls below the target lower level.Alternatively, or in addition, the speed of the nutrient pump 182 can bevariable and can be controlled by the controller to vary and control therate at which nutrients are added into the perfusate. One of thenutrients which can be detected by the BGA 192 and controlled in thisway is glucose. However one or more other nutrients can also becontrolled in the same way,

The controller 18 is also arranged to monitor the signal from the bubbledetector 113 during perfusion and, if it detects the presence of gasbubbles in the perfusate, or more than a minimum bubble content in theperfusate, the controller 18 is arranged to close the pinch valve 112 asdescribed above. The controller 18 can also be arranged to display awarning on the GUI 17 if bubbles are detected.

The surrogate organ 126 is already connected into the circuit as part ofthe disposable set, as is the oxygenator 14, and the pump 123. Theperfusion circuit is then filled with perfusate. To achieve this, theflow control valves 112, 146 in the portal duct 100 and pressure controlduct are opened A perfusion bag 194 containing perfusate is connected tothe upper end of the priming duct 196. The priming bag 194 is thenraised to a level that is higher than top of the fluid reservoir 12.This causes perfusate fluid from the priming bag to flow into theperfusion circuit at the priming point 104 a in the vena cava duct 104,and flow upwards through the whole perfusion circuit from that point. Asthe fluid level in the perfusion circuit rises, this fills the vena cavaduct 104, the surrogate organ 126, the hepatic artery duct 102 and theportal duct 100, the through duct 150 of the oxygenator, and thepressure control duct 142, and the reservoir 12, with the ports 82, 178in the top of the reservoir being used to vent air out of the system asit fills. The pump head can be independently moved and tapped relativeto is driving motor to enable removal of any gas trapped within the pumphead during filling

When the perfusion circuit 16 has been filled, the ascites duct isconnected to the ascites return port 82 in the reservoir and thenutrient feed duct 174 is connected to the nutrient feed port 178 in thereservoir, and the vent 158 from the oxygenator 14 is closed. The systemis then switched on, for example by a user inputting a start commandusing the GUI 17 and starts to run and the controller 18 is arranged tocontrol the system as follows. When the system starts to run, both thepressure control valve 146 and the flow control valve 112 in the portalvein duct are opened. Initially, therefore, the pump 123 pumps fluidthrough the hepatic artery duct 102, through the portal vein duct 100,through the surrogate organ 126, and through the IVC duct 104, alsoensuring constant circulation of the perfusion fluid within thereservoir 12. The controller 18 is arranged initially to control thepump 123 to operate at a constant speed and to monitor the pressures inthe hepatic artery duct 102 and the IVC duct 104 and compare them. Sincethe surrogate organ 126 is present, the pressure drop across it is low,in particular significantly lower than what it would be if a real organwere connected into the circuit, and this enables the controller 18 todetect the presence of the surrogate organ from the outputs from thedifference between the pressures measured by the pressure sensors 136,138.

In a modification to this embodiment, just one of the two measuredpressures can be used to detect the presence of the surrogate organ 126.For example the surrogate organ may be determined as being present (orthe real organ as being absent) provided the pressure in the hepaticartery duct remains below a predetermined value. In another alternativemodification, the measured fluid flow rate at at least one point in thecircuit, for example in the fluid removal duct 104 as measured by theflow sensor 125, or in the second fluid supply duct 102, can be used,either on its own or in combination with data defining the speed of thepump 123, to determine whether the organ is present in the circuit. Thisis because flow rates will be slower generally, and more specificallywill be slower for any given pump speed, when the organ is present thanwhen it is not. This is because the organ provides a greater resistanceto fluid flow, which can be measured by measuring the fluid flow rate.

While the surrogate organ is present, and in particular while thecontroller 18 detects that the surrogate organ is present, thecontroller 18 operates in a preparation mode it which it is preparingthe system for connection of the real organ. In this mode, thecontroller 18 is arranged to control the pump 123 so that it pumps fluidthrough the oxygenator at a constant flow rate, and monitor and adjustthe various parameters of the fluid, as described above, so as to bringthem within target ranges suitable for perfusion of a real organ. Thetarget ranges for each of the parameters may be entered into the systemby a user via the GUI 17, or may be set as a default value. The bubblecontent of the perfusate can also be considered as one of the parametersthat is monitored by the controller using the bubble detector 145. Whenthe system is first started up it is possible that some gas bubbles arepresent in the perfusate. The controller 18 is arranged to monitor fortheir presence and to check whether the bubble content is within apredetermined target range, which is typically defined solely by amaximum acceptable value, which may be zero. When the perfusateparameters have reached the target values, the system is ready forconnection of the real organ. The controller 18 may be arranged todetect the reaching of all target ranges or values, and to provide anindication, via the GUI 17, that the system is ready.

To enable connection of the real organ, the pump 123 is stopped. The GUI17 allows a user demand to be input to the controller 18 to stop thepump 123. When this demand is received by the controller, the controlleris arranged to stop the pump 123 so that circulation of the perfusatestops. The surrogate organ 126 is then disconnected from the circuit,and the organ 250 connected into the circuit as shown in FIG. 5. Thecontroller is arranged, when it receives a ‘start’ demand from a user,input via the GUI 17, to start the pump 123 at a constant rate again,and again to monitor the pressures in the hepatic artery duct 102 andthe IVC duct 104 and compare them. Now, as the real organ 250 provides asignificant resistance to perfusate flow, a pressure differential willquickly build up across the organ 250. Specifically the pressure in thehepatic artery duct 102 increases as perfusate is pumped into it, andthe pressure in the IVC duct 104 decreases as perfusate is pumped awayfrom it. When the controller detects that the difference between thepressures in those two ducts reaches a predetermined level, thisprovides an indication that the real organ 250 is connected into thecircuit and the controller switches to a perfusion mode. In theperfusion mode the controller 18 is arranged to control the pressure inthe hepatic artery duct 102 and the IVC duct 104, by controlling thespeed of the pump 123 and the degree of opening of the pressure controlvalve 146 as described above, to maintain them within predeterminedtarget pressure ranges. As mentioned above, the presence of the realorgan can be detected by detecting simply when the pressure in thehepatic artery duct 102 reaches a predetermined level.

With the real organ 250 present, the controller 18 is arranged to startto measure the volume of bile using the bile measurement system 62 asdescribed above. It is also arranged to start draining ascites from thesump 26, and measuring the volume of that ascites, as described above.The controller is also arranged to record the total number times thatthe bile measurement system valve 76 is opened and the total number oftimes that the ascites pump 84 is activated to measure the total volumeof bile and the total volume of ascites that are produced by the liverduring perfusion. It is also arranged to measure the time between eachpair of subsequent operations of the valve 76, and each pair ofsubsequent operations of the pump 84, and to calculate for each pair ofoperations, an associated flow rate of bile, and an associated flow rateof ascites, from the liver.

It will be appreciated that, if an organ other than the liver isconnected into the system, the bile measurement system and the ascitesmeasurement system can each be used to measure different fluids asproduced by that organ. For example they can be used to measure urinefrom a kidney. Also in another embodiment of the system, a measurementsystem which is the same as the bile measurement system 62 describedabove is included in the ascites duct 80 upstream of the pump 84 to givea more accurate measurement of ascites.

In a still further embodiment, the bile measurement system 62 isprovided without the rest of the perfusion system described above, andcan then be connected to an organ, such as a liver, during surgery, tomeasure the volume or flow rate of fluid produced by the organ duringsurgery.

Referring to FIG. 6, the system of FIG. 1 can be modified for perfusionof a pancreas, or other organ with only one vein and one artery thatneed connection to the perfusion circuit. The only significantmodification is that the downstream end of the first fluid supply duct100 is not connected to the organ, but instead is connected to the fluidremoval duct 104 just upstream of the pump 123. The other two ducts areconnected to the organ in the same way as for the liver: the secondfluid supply duct 102 is connected to the organ to supply perfusionfluid to the organ, and the fluid removal duct 104 is connected to theorgan to carry perfusion fluid from the organ. When the organ is notpresent, the circuit can be completed using a surrogate organ 126′ whichin this case is a simple length of conduit having an inlet end and anoutlet end, each of which has a connector on it so that they can beconnected to the second connector 116 and the third connector 120respectively. Operation of the system in this configuration is the sameas that described above with reference to FIG. 1, and will not bedescribed again in detail, except that fluid flow from the reservoir 12through the first duct 100 simply replaces fluid that flows through thepressure relief duct 142 back to the reservoir. For the pancreas thebile sump and measurement system is not used, whilst any fluid leaked bythe organ can still be collected and re-circulated using fluid sump 24.

Referring to FIGS. 7 a, 7 b, and 7 c, in one embodiment the whole of thesystem of FIG. 1, or FIG. 6, is mounted on a support stand 700 which isstowable within a transport trolley 702. The trolley 702 has a flatsubstantially rectangular base 704 supported on four wheels or castors705, and four side walls 706 each extending upwards from the base anddefining a storage volume within the walls. The stand 700 comprises avertical side wall 708, a shelf 710 projecting horizontally from thebottom edge of the side wall, towards one end of the side wall, and arectangular support panel 712 which is inclined against the other end ofthe side wall. The support panel 712 is included at about 30° to thevertical, with its upper end parallel to, and joined to, the upper edgeof the side wall 708 and its lower edge spaced from the side wall 708 bya distance equal to the width of the shelf 710. The bottom of thesupport stand 700 is therefore rectangular with one half being formed bythe shelf 710 and the other half being the open lower end of a cavity713 formed between the inclined support panel 712 and the side wall 708.The support stand 700 further comprises a top panel 714 which extendshorizontally from the top edge of the side wall. The top panel 714 andthe bottom of the support stand are of equal size and both arranged tofit inside the storage volume within the trolley. The GUI 17 is mountedin the top panel 714 of the support stand, and can be raised for use asshown in FIG. 7 a or lowered for storage as shown in FIG. 7 b. Thesystem can further comprise a detachable hand-held display 720 which canbe arranged to communicate wirelessly with the controller 18 andarranged to display the same information as the GUI 17 and to include afurther user input to enable a user to input the same data as can beinput via the GUI 17.

The support stand 700 is mounted within the trolley 702 on a liftingmechanism (not shown) which allows the support stand 700 to be movedbetween a stored position, or transit configuration, as shown in FIG. 7b, in which the top panel 714 is flush with the top of the trolleywalls, and a raised position, or surgery configuration, as shown inFIGS. 7 a and 7 c, in which the bottom of the support stand 700 is levelwith the top of the trolley walls. As shown in FIGS. 7 a and 7 c, one ormore oxygen bottles 722 and a battery 724 can be stored within thetransport trolley, supported on its base 704, and located so that theyare within the cavity 713 inside the support stand 700 when the supportstand is in the lowered position.

Referring to FIGS. 8 a, 8 b, and 8 c, in a further embodiment thetransport is similar to that of FIGS. 7 a, 7 b and 7 c, except that thesupport stand 800 is not connected to the trolley 802 but simply restson the wheeled base 804 when the system is in the transit configurationas shown in FIG. 8 b. Also the support stand includes a base panel 810which forms whole of the lower end of the support stand, with a verticalwall 808 extending upwards from the base panel 810 parallel to its endsand about half way along it. The base panel 810 therefore forms theshelf on one side of the vertical wall 808, and on the other side formsa base below a cavity between the support panel 812 and the centralwall, on which the oxygen bottle or other items can be located. Thesupport panel 812 has its lower edge along one end of the base panel810, and is inclined against the vertical wall 808. A cover comprisesside walls 806 and a top panel 814, and is arranged to fit over thesupport stand 800 with its lower edge resting on the trolley 804 in thetransit configuration. A seal is provided between the cover and the baseto seal the transfusion system inside. To use the transfusion system,the cover is simply lifted off the base 804, the cover 806, 814 isreplaced on the base, and the support stand 800 is then rested on thetop panel 814 of the cover as shown in FIG. 8 c.

Referring to FIGS. 9 a, 9 b, 9 c and 9 d, in a transport systemaccording to a further embodiment of the invention, the support stand900 is similar to that of FIG. 7 a, but the trolley 902 is of aclam-shell design, comprising a wheeled base 904 and two cover sections906 a, 906 b each of which is hinged to the base 904 along a respectiveside of the base. Each of the cover sections 906 a, 906 b comprises aside panel 930, the bottom edge of which is hinged to the base 904, andtwo end portions 932 and a top portion 914. When the cover is closed asshown in FIG. 9 a, the side panels 930 are substantially verticaldefining a cavity between them, and the to portions 914 extend over thetop of the cavity to meet each other and the end portions 932 at eachend of the cover extend across the side of the cavity to meet eachother. The cavity is therefore sealed between the two cover sections 906a, 906 b and the support stand can be contained inside the cover. Toremove the transfusion system from the cover, the two cover sections 906a, 906 b are opened and the support stand 900 which supports thetransfusion system is simply lifted out of the cover, and can be place,for example, on a table for use.

Referring to FIG. 10, a transport system according to a furtherembodiment of the invention comprises a support stand 1000, a wheeledtrolley 1002, and a cover 1006. The trolley 1002 is formed from a framestructure 1002 a and a plastic moulding 1002 b. The moulding 1002 brests on part of the frame structure 1002 a to form the base 1004 of thetrolley, and part 1002 c of the frame structure forms a handle forpushing the trolley which can be folded for easy stowing of the trolley.The support stand 1000 is arranged to rest on the base 1004 of thetrolley, and comprises a base panel 1010 one half of which forms a shelf1011 and the other half of which supports a support tower 1013, one face1012 of which supports the perfusion circuit 16, the reservoir 12, theGUI 17, the pump 123, and the syringes 172. The cover 1006 comprisesside walls and a top panel 1014, and is arranged to fit over the supportstand 1000, and seal against its base 1010, to cover and protect theperfusion system. For transportation the support stand 1000 is placed onthe base of the trolley 1002, and the cover 1006 is place over it. Whenthe perfusion system is to be used, the cover 1006 is lifted off, andthe support stand 1000 with the perfusion system mounted on it is liftedoff the trolley and placed on a table or similar support.

1. A perfusion system for perfusing an organ, the system comprising: aperfusion fluid circuit arranged to circulate perfusion fluid throughthe organ; a surrogate organ arranged to be connected into the circuitin place of the organ so that the circuit can circulate fluid throughthe surrogate organ; and organ sensing means arranged to distinguishbetween the presence of the organ in the circuit and the presence of thesurrogate organ in the circuit.
 2. A system according to claim 1 whereinthe organ sensing means comprises at least one pressure sensor arrangedto measure the pressure of the perfusion fluid at at least one point inthe circuit.
 3. A system according to claim 2 wherein the organ sensingmeans is arranged to measure the difference in pressure between twopoints in the circuit.
 4. A system according to claim 2 or claim 3wherein the organ sensing means comprises one pressure sensor arrangedto measure the pressure of perfusion fluid flowing towards the organ,and one pressure sensor arranged to measure the pressure of perfusionfluid flowing away from the organ.
 5. A system according to anyforegoing claim wherein the organ sensing means comprises a flow meterarranged to measure the rate of fluid flow at at least one point in thecircuit.
 6. A system according to any foregoing claim wherein thecontrol means is arranged to operate in two different modes, one ofwhich is a perfusion mode suitable for perfusion of an organ and one ofwhich is a preparation mode suitable for preparing the system forperfusion of an organ.
 7. A system according to claim 6 wherein thecontrol means is arranged, in both of the modes, to control the contentof at least one component of the perfusion fluid, but to control thefluid flow in the perfusion circuit in a different way in each of thetwo modes.
 8. A system according to any foregoing claim furthercomprising adjustment means for adjusting the content of at least onecomponent in the fluid, measuring means for measuring the content ofsaid at least one component in the perfusion fluid, and control meansarranged to control the adjustment means so as to keep said measuredcontent within a target range.
 9. A perfusion system for the perfusionof an organ, the system comprising a perfusion fluid circuit forcirculating perfusion fluid through the organ, adjustment means foradjusting the content of at least one component in the fluid, measuringmeans for measuring the content of said at least one component in theperfusion fluid, and control means arranged to control the adjustmentmeans so as to keep said measured content within a target range.
 10. Aperfusion system according to claim 9 wherein the at least one componentis at least one of: oxygen; carbon dioxide; and a nutrient.
 11. Aperfusion system according to claim 8 or claim 9 wherein the at leastone component comprises oxygen, and the adjustment means comprisesoxygen adding means arranged to add oxygen into the fluid.
 12. Aperfusion system according to any of claims 7 to 11 wherein the at leastone component comprises carbon dioxide, and the adjustment meanscomprises carbon dioxide extraction means arranged to extract carbondioxide from the fluid.
 13. A perfusion system according to any ofclaims 7 to 12 wherein the at least one component is at least one of:oxygen and carbon dioxide; the system further comprising nutrientmeasuring means arranged to measure the content of at least one nutrientin the fluid, a nutrient supply, and nutrient adding means arranged toadd the nutrient from the supply into the fluid, wherein the controlmeans is arranged to control the nutrient adding means to add thenutrient if the content of the nutrient falls below a target range. 14.A perfusion system according to any of claims 7 to 13 further comprisinga thermometer arranged to measure the temperature of the fluid, andthermal adjustment means arranged to adjust the temperature of thefluid, wherein the control means is arranged to control the thermaladjustment means to maintain the temperature of the fluid within atarget range.
 15. A perfusion system according to any of claims 7 to 14further comprising an analysis duct through which the fluid can flow,wherein the measuring means is arranged to measure the fluid in theanalysis duct.
 16. A perfusion system according to any of claims 7 to 15wherein the measuring means is arranged to operate during perfusion ofthe organ and the control means is arranged to operate during perfusionof the organ to maintain the target range or ranges.
 17. A perfusionsystem according to any of claims 7 to 16 wherein the control meansincludes a memory arranged to store at least one limit of said range, orof at least one of said ranges, and the control means is arranged tocompare the measured content with said at least one limit.
 18. Aperfusion system according to any of claims 7 to 17 further comprising auser interface arranged to enable a user to input at least one limit ofsaid range, or of at least one of said ranges.
 19. A system according toany foregoing claim further comprising a bubble detection means arrangedto detect bubbles in the fluid during perfusion, wherein the controlmeans is arranged to respond to detection of bubbles by the bubbledetection means.
 20. A perfusion system comprising a circuit forcirculating perfusion fluid through the organ, control means arranged tocontrol the flow of fluid round the perfusion circuit, and bubbledetection means arranged to detect the presence of bubbles in the fluid,wherein the control means is arranged to respond to detection of bubblesby the bubble detection means.
 21. A system according to claim 19 orclaim 20 wherein the control means is arranged to respond to detectionof the bubbles by at least one of: producing a warning output, andreducing the fluid flow through at least one part of the circuit.
 22. Asystem according to any of claims 19 to 21 wherein the bubble detectionmeans is arranged also to measure the flow rate of fluid in theperfusion circuit.
 23. A system according to any of claims 19 to 22wherein the bubble detection means comprises an ultrasound transducer.24. A system according to claim 23 wherein the bubble detection means isarranged to determine both whether bubbles are present in the fluid andthe flow rate of the fluid from the timing of ultrasound transmissionsand detections.
 25. A system according to any foregoing claim furthercomprising measuring means arranged to measure the amount of fluidsecreted by or leaked from the organ.
 26. A system according to claim 25further comprising a sump arranged to collect the secreted or leakedfluid, wherein the measuring means is arranged to measure the volume offluid that enters the sump.
 27. A system according to claim 25 or claim26 which is arranged to record and display the amount of fluid that issecreted or leaked.
 28. A system according to any foregoing claimfurther comprising a support stand on which at least some of thecomponents of at least one of the perfusion circuit, the adjustmentmeans and the control means are mounted, and a transport system on whichthe support stand can be mounted, wherein the transport system includesa cover arranged to cover the support stand and the components mountedon it.
 29. A system according to claim 28 wherein the transport systemincludes a wheeled base.
 30. A system according to claim 27 or claim 28wherein the transport system is arranged to support the support stand intransport position, or an operative position which is raised relative tothe transport position.
 31. A system according to any or claims 25 to 27wherein the measuring means comprises a fluid collection volume, sensingmeans arranged to detect when a predetermined volume of the fluid hascollected in the collection volume, and control means arranged to removethe fluid from the collection volume when said predetermined volume isreached.
 32. A system according to claim 31 wherein the control means isarranged to record each occurrence of the predetermined volume beingreached thereby to record the total volume of the fluid flowing from theorgan.
 33. A system according to claim 32 wherein the control means isarranged to determine the time between subsequent occurrences of thepredetermined volume being reached.
 34. A system according to claim 33wherein the control means is arranged to determine, from said time, aflow rate of the fluid from the organ.
 35. A system according to any ofclaims 31 to 34 further comprising display means arranged to displayinformation relating to the amount of the fluid that flows from theorgan.
 36. A system according to claim 35 wherein the display means isarranged to display a flow rate of the fluid.
 37. A system according toclaim 35 or claim 36 wherein the display means is arranged to display atotal volume of the fluid.
 38. A system according to of claims 31 to 37wherein the measuring means further comprises an outlet from the fluidcollection volume and a valve in the outlet, wherein the control meansis arranged to open the valve to remove the fluid from the collectionvolume.
 39. A system according to any of claims 31 to 38 wherein themeasuring means comprises a level sensor arranged to sense when thefluid in the collection volume reaches a predetermined level.
 40. Asystem according to any of claims 31 to 39 wherein the measuring meanscomprises a pump and the control means is arranged to operate the pumpto remove the fluid from the collection volume.
 41. A system accordingto any of claims 31 to 40 comprising an inlet duct, an outlet duct andan overflow duct connected together.
 42. A system according to claim 41wherein the collection volume is defined at least partly within theinlet duct.
 43. A system according to claim 41 or claim 42 wherein thecollection volume is defined at least partly within the overflow duct.44. A system according to any of claims 41 to 43 wherein the measuringmeans is arranged to detect the level of the fluid in at least one ofthe inlet duct and the overflow duct.
 45. A system according to any ofclaims 41 to 44 further comprising a sump wherein the outlet duct andthe overflow duct are both connected to the sump.
 46. A system accordingto any of claims 41 to 45 further comprising a connector for connectingthe measuring means via a cannula to the organ.
 47. A method ofmeasuring fluid flowing from an organ, the method comprising collectingthe fluid in a fluid collection volume, detecting when a predeterminedvolume of the fluid has collected in the collection volume, and removingthe fluid from the collection volume when said predetermined volume isreached.
 48. A method according to claim 47 further comprising recordingeach occurrence of the predetermined volume being reached thereby torecord the total volume of the fluid from the organ.
 49. A method systemaccording to claim 48 comprising determining the time between subsequentoccurrences of the predetermined volume being reached.
 50. A methodaccording to claim 49 comprising determining, from said time, a flowrate of the fluid from the organ.
 51. A method according to any ofclaims 47 to 50 wherein the fluid is bile, or urine, or ascites, orinterstitial fluid.
 52. A measuring system for measuring the amount offluid flowing from an organ, wherein the system comprises a fluidcollection volume, sensing means arranged to detect when a predeterminedvolume of the fluid has collected in the collection volume, and controlmeans arranged to remove the fluid from the collection volume when saidpredetermined volume is reached.